Networked concave microwell arrays for constructing 3D cell spheroids
Open accessAbstract
The engineered three-dimensional (3D) cell cultivation system for the production of multicellular spheroids has attracted considerable attention due to its improved in vivo relevance to cellular communications compared with the traditional two-dimensional (2D) cell culture platform. The formation and maintenance of cell spheroids in a healthy condition is the critical factor for tissue engineering applications such as the repair of damaged tissues, the development of organ replacement parts and preclinical drug tests. However, culturing spheroids in conventional isolated single wells shows limited yield and reduced maintenance periods due to the lack of proper supplies of nutrition as well as intercellular chemical signaling. Here, we develop novel networked concave microwell arrays for the effective construction of 3D multi-cellular spheroids. The proposed method provides a suitable structure for the diffusion of oxygen, water-soluble nutrients and cytokines for cell–cell interactions between the spheroids in neighboring microwells. We have further demonstrated that hepatocyte spheroid cultured networked concave microwells show enhanced cell viability and albumin secretion compared to the un-networked control group over two weeks. Our results reveal that multi-cellular functionality can be tuned up by networking individual 3D spheroids without supplying additional chemicals or biological supplements. We anticipate our result to be useful in high-throughput cellular screening platforms to study cell–cell interactions, in response to diverse chemical stimuli as well as the development of the in vivo mimicking of the customized 3D tissue culture system.
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A number of groups were able to generate spheroids in chip-based devices, but the spheroids lack spatial complexity and cell types compared to fully-developed organoids.
“A number of groups were able to generate spheroids in chip-based devices171–173, but the spheroids lack spatial complexity and cell types compared to fully-developed organoids.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [172]
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- Wong S F, No da Y, Choi Y Y, Kim D S, Chung B G and Lee S H 2011 Concave microwell based size-controllable hepatosphere as a three-dimensional liver tissue model Biomaterials 32 8087-96 · DOI
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Self-citation
- Authors
- Lee, G. H., Lee, J. S., Lee, G.-H., Joung, W. Y., Kim, S. H., Lee, S. H., Park, J. Y., & Kim, D.-H.
- Affiliations
- Korea University (KR)
- Korea Institute of Science and Technology (KR)
- Chung-Ang University (KR)
- Corresponding author
- Kim, Soo Hyun
- Park, Joong Yull
- Kim, Dong-Hwee
- Venue
- Biofabrication
- Publisher
- IOP Publishing
- Published
- 2017-11-30
- Volume
- 10
- Issue
- 1
- Pages
- 015001
- ISSN
- 1758-5082 (ISSN-L)
- 1758-5090
- OpenAlex
- W2767521020
- Cited by
- 47
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 13 · 2019: 7 · 2018: 5
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biofabrication (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (R1610511)
- KU-KIST School Project (R1435293)
- Korea University Future Research Grant (K1614471)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- multicellular spheroids, hepatocyte spheroids, cell-cell interactions, nutrient diffusion, oxygen diffusion, albumin secretion, cell viability, 3D cell culture, tissue engineering
- MeSH terms
- Albumins, Animals, Cell Communication, Cell Survival, Cells, Cultured, Diffusion, Male, Microscopy, Fluorescence, Cytokines, Rats, Sprague-Dawley, Spheroids, Cellular, Cell Culture Techniques, Hepatocytes, Tissue Engineering, Rats
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